1. Field of the invention
The present invention relates to topical composition and methods for the prevention and treatment of viral infections, such as Herpes and AIDS.
2. Background of the Related Art
Sexually transmitted diseases such as Herpes and AIDS remain frustrating, distressing and unyielding infections. Patients continually suffer their disease and in the case of AIDS, the patient ultimately succumbs and gives up his or her life. Because these diseases socially brand patients once they are infected with these envelope viruses, it is not only important to reduce the level of these viruses in the infected patients, but it is also important to protect non-infected individuals from acquiring these viruses. Thus in one case, treatment is necessary to stabilize the patients while in non-infected individuals, prevention is imperative.
At the present time, there are a limited number of small molecular weight drugs which are either being used therapeutically or are currently being tested in antiviral chemotherapy. The majority of these drugs are derivatives of nucleosides, although in recent years with the development of AIDS, other types of drugs, for example, peptides have been undergoing rigorous testing as potential antivirals. The peptides are geared to block viral penetration of human cells while the nucleosides exert their antiviral effects by penetrating viral-infected mammalian cells, thus interfering inside the cell with nucleic acid synthesis.
To date, the failures of antiviral chemotherapy can be attributed in part to a lack of selective toxicity, in part to the development of chronic resistance to antiviral drugs and in part to the recurrence of infection once drug therapy has been terminated. In the case of Herpes, recurrence of infection is exacerbated by the latency of the virus which emerges insidiously from its home in the ganglia of nerve cells to cause infection. This is also true for the HIV-1 virus (the AIDS virus) which not only hides in an inactive form in the host chromosome but also is proving more and more elusive and resistant even when patients are given powerful drugs such as azidothymidine (AZT).
As an alternative to prescription antiviral drugs which have toxic side effects, it would be desirable to develop an inexpensive, safe combination of simple ingredients that would be used as a potent over-the-counter antiviral formulation. Although a number of simple chemicals will inactivate both the Herpes and AIDS virus, as well as other viruses, these chemicals for the most part are not safe for human use and are generally employed for the disinfection of biological samples and tissue; See for example Yash et al., American Clinical Laboratory, 23-32 (October 1990).
To protect both infected and non-infected individuals, it is the belief of the inventors, herein, that a daily regimen of an appropriate antiviral formulation is required Since it is believed that this formulation should be given long-term on a continuous basis without interruption, then a simple safe over-the-counter formulation would be ideal for both treatment and prevention of viral disease. In the case of a mouthrinse, which has only a limited time period in the oral cavity, antiviral activity should be accomplished within a minute of contact with virus. This would also be true of vaginal douches, but would be less important, for example, with vaginal and rectal creams which can be formulated to remain longer at the site of the infection.
Chlorhexidine at 0.2% is known as being an effective antibacterial germicidal and has been shown to exert moderate Herpes antiviral activity, Park et al., Oral Surg. Oral Med. and Oral Path., 67, 149-153 (1989). However, Chlorhexidine has an unpleasant bitter taste and characteristically stains both tooth enamel and skin a brown color. Very dilute concentrations of chlorhexidine, i.e. about 0.05% on the other hand, are not known to be effective anti-viral agents.
Various compositions containing chlorhexidine are present in the prior art. For example, chlorhexidine is contained in an oral rinse germicidal composition sold under the name PERIDEX.RTM.. It contains a 0.12% chlorhexidine gluconate in a base containing water, 11.6% alcohol, glycerine, PEG-40 sorbitan disostearate, flavor, sodium saccharine, and FD&C Blue No. 1. There are a various patents which describe the use of Chlorhexidine for its antibacterial/antifungal germicidal activity, see U.S. Pat. Nos. 3,956,480, 4,759,925, 4,915,936, and 4,980,150.
Other compositions that are described as being antiviral, specifically the treatment of herpes virus infection are disclosed in U.S. Pat. No. 4,661,493 to Gibbs. Gibbs describes topical vaginal forms of tioconazole and related antimicrobic compounds, especially miconazole, econazole, clotrimazole, butaconazole and ketoconazole for being useful in controlling Herpes virus infections. A variety of representative formulations are described on Col. 4 of the patent, for example tioconazole vaginal tablets containing 100mg per tablet of tioconazole and 1.20mg per tablet of sodium lauryl sulfate in a total formulation weighing 1,128mg. Tioconazole cream containing propylene glycol, ointment containing tioconazole and paraffin, and tioconazole vaginal ovals containing tioconazole and glycine as the primary components are also described.
The inventors herein in U.S. Pat. No. 4,863,900 describe a method for reducing viral transmission of HSV-1 and HSV-2 infections using compositions containing poly-L-histidine. The compositions include a topically applicable, pharmaceutically acceptable carrier and a viricidally effective amount of a polypeptide of between 24 and 500 aminoacid residue; containing at least 24 residues of L-histidine. These compositions are described as generally applicable to Herpes infections of the mucosa, such as eye infection, oral infection and vaginal infection; and viral infection of non-mucosa tissues, in particular border areas such as lips and rectum as well as the skin. The patent recites that all envelope viruses are considered within the scope of the invention but especially herpes simplex virus such as HSV-1 or HSV-2. A variety of formulations containing the poly-L-histidine compound in approximately a 10% concentration are disclosed at columns 4-10 of the patent. For example, a toothpaste formulation is described as containing poly-L-histidine, carboxymethyl cellulose, glycerine, propylene glycol and sodium lauryl sulfate; and a mouthwash formulation is described as containing approximately 10% poly-L-histidine and approximately 10% each glycerine and water. Poly-L-histidine is the active anti-herpes antiviral agent of this patent and without it the composition lacks any antiviral activity. More importantly, poly-L-histidine is not effective against the AIDS virus.
Other medicaments described as useful for the treatment of bacterial, viral or fungicidal inflammation of the oral cavity are disclosed in U.S. Pat. No. 4,981,875 to Lausner et al. The medicaments described by Lausner et al. are adhesive emulsions containing etofenate, a suitable carrier, a swellable hydrophilic polymer, flavorings, preservatives and colorants, as well as other active compounds which can be included, such as anesthetics chemotherapeutics, antibiotics, disinfectants and astringents. The effectiveness of this medicament in the treatment of viral infections such as Herpes, AIDS and other envelope virus infections is not disclosed.
Accordingly, there is an urgent need for topical compositions and methods for the prevention and treatment of envelope viral infections such as Herpes and AIDS, which can be applied topically without the above-mentioned drawbacks of the compositions of the prior art.